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Maria R. Parkhurst, Ph.D.

Surgery Branch
Head, Antigen Discovery Core Facility
Staff Scientist
Center for Cancer Research
National Cancer Institute
Building 10 - Hatfield CRC, Room 4-5744
Bethesda, MD 20892
Phone:  
301-435-3026
Fax:  
301-496-0011
E-Mail:  
parkhurm@mail.nih.gov

Biography

Dr. Parkhurst earned a B.S. in Chemical Engineering from the University of Maryland and subsequently a Ph.D. in Chemical Engineering from the Johns Hopkins University. During her Ph.D. studies, she was awarded a Howard Hughes Medical Institute predoctoral fellowship and studied leukocyte migration in mucus and interaction with mucosal epithelia. She then completed a postdoctoral fellowship in the Surgery Branch of the NCI and worked on developing and monitoring T cell epitope tumor vaccines. She then became a staff scientist in the Surgery Branch of the NCI as the manager of the Peptide Synthesis Core Facility. Since that time, the clinical pursuits of the Surgery Branch have shifted from peptide vaccines to treating patients with adoptively transferred T lymphocytes. As such, Dr. Parkhurst is now the manager of the Antigen Discovery Core whose primary responsibilities are to generate new populations of tumor reactive T lymphocytes and identify new tumor reactive T cell receptors for use in gene therapy clinical trials.

Research

The Antigen Discovery Core facility provides services to Surgery Branch investigators related to the identification of tumor associated epitopes and the generation of tumor reactive T lymphocytes for adoptive transfer, most notably through the identification of tumor reactive TCRs. This process involves multiple steps and technical challenges, and the Antigen Discovery Core facility has the technical expertise to assist and/or provide services associated with each step as follows:

Step 1: Identification of candidate tumor antigens and epitopes
Step 2a. In vitro stimulation of human peripheral blood lymphocytes (PBLs) with tumor associated peptides
Step 2b. Immunization of HLA transgenic mice with human tumor antigens and in vitro stimulation of lymph node cells or splenocytes
Step 3. Evaluation of T cell function
Step 4. Isolation of TCR alpha and beta chains from reactive clones
Step 5. Introduction of TCR alpha and beta chains into human T cells by either RNA electroporation or retroviral transduction and subsequent functional evaluation
Step 6. Modification of TCR alpha and beta chains to improve function
Step 7. Transduction and expansion of large numbers of T cells for patient treatment

Over the last 10 years, the Antigen Discovery Core has led efforts to develop multiple tumor reactive TCRs for use in gene therapy trials as follows:

HLA-A*0201 restricted CEA reactive TCR: This TCR was used in a clinical trial to treat patients with metastatic colorectal cancer.
HLA-A*0201 restricted MAGE-A3 reactive TCR: This TCR was used in a clinical trial to treat patients with metastatic cancers.
HLA-A*0201 restricted NY-ESO-1 reactive TCR: A clinical grade retroviral supernatant encoding this TCR has been made and is awaiting use in a clinical trial.
HLA-DRbeta1*0401 restricted tyrosinase reactive TCR: A clinical grade retroviral supernatant encoding this TCR has been made and is awaiting use in a clinical trial.
HLA-DPbetat1*0401 restricted MAGE-A3 reactive TCR: A clinical grade retroviral supernatant encoding this TCR has been made and is awaiting use in a clinical trial.
HLA-DRbeta1*0401 restricted gp100 reactive TCR: A retroviral vector encoding this TCR has been constructed and evaluated in pre-clinical assays.
HLA-DPbeta1*0401 restricted NY-ESO-1 reactive TCR: A retroviral vector encoding this TCR has been constructed and evaluated in pre-clinical assays.
HLA-A*0201 restricted NY-BR-1 reactive TCR: A retroviral vector encoding this TCR has been constructed and is currently being evaluated in pre-clinical assays.
HLA-A*0201 restricted WT1 reactive TCR: A retroviral vector encoding this TCR has been constructed and is currently being evaluated in pre-clinical assays.

In addition, we have led efforts to identify HLA-A2 restricted tumor reactive TCRs specifically reactive with the following antigens: MAGE-A1, MAGE-A3 (epitopes other than MAGE-A3:112-120 referred to above), SSX2, Survivin, CEA (epitopes other than CEA:691-699 referred to above), hTERT, PRAME, Mammaglobin-A, MMP11, VEGFR2, and mutated antigens identified by exome and RNA sequencing of tumor cells. However, these efforts have not yet been pursued clinically because we have not yet been able to identify T cell populations that recognize naturally processed epitopes from these antigens.

This page was last updated on 3/14/2014.